Encephalomyocarditis (EMC) viruses cause a diabetes mellitus-like disease in DBA/2 mice. Virus grows rapidly in the beta cells of the islets of Langerhans of infected animals, reaching maximal concentrations on day 3 and decreasing thereafter. Insulities and beta cell injury are apparent on day 6 in normal infected mice, but are absent in T lymphocyte deficient animals, suggesting that T lymphocytes are important in this disease. T lymphocytes have a number of immune functions including 1) helper activity in IgG antibody production, 2) direct effector cell mediated cytolysis of beta cells, and 3) activation of nonspecific effector cells such as macrophage. The specific aims of this proposal are to investigate which T cell functions are primarily important in the pathogenesis of EMC virus-induced diabetes. This will be done by identifying the lymphoid cells intemately associated with beta cell degradation and insulin release in the infected islet and by restoration of insulitis and beta cell necrosis in thymectomized, irradiated, bone marrow-reconstituted animals with adaptively transferred helper Lyt1+) or effector (Lyt2+) T lymphocytes, B cells or macrophage from diabetic animals. By determining the immunological mechanisms underlying experimental viral diabetes we hope to ultimately provide information and procedures applicable to the prevention or treatment of the clinical disease.